医学交流课件：PortalHypertensiveBleedinginCirrhosis

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1、Portal Hypertensive Bleeding in Cirrhosis: Risk Portal Hypertensive Bleeding in Cirrhosis: Risk Stratification, Diagnosis and Management -Stratification, Diagnosis and Management -contents01Purpose and Scope of the Guidance02Risk Stratification03Epidemiology and Associated Conditions04Pathophysiolog

2、ical bases of therapy05Diagnosis and Monitoring07Gastric varices08Ectopic varices09Special populations10Suggestions for Future Research06Management静脉曲张分型的供血基础01 Purpose and Scope of the Guidance not a guideline They are intended to be in contrast to formal treatment recommendations or standards of c

3、are, which are inflexible policies designed to be followed in every pensated cirrhosisAdecompensated cirrhosisB02 Risk Stratificationthe presence or absence of clinically evident decompensating events ()The Child-Turcotte-Pugh (CTP) classification has been used to stratifypatients with cirrhosis. Pa

4、tients with cirrhosis belonging to class are compensated, while those inclass are mostly decompensated.median survival12 years1.8 years03 Epidemiology and Associated Conditions GEV are present in approximately of patients with cirrhosis -compensated cirrhosis -decompensated cirrhosis Variceal hemorr

5、hage occurs at a rate of around per year which is now recognized as the primary endpoint to assess the impact of therapies for acute variceal hemorrhage, ranges between 15% and 25%04 Pathophysiological bases of therapyNon-invasive tests (NIT) in the diagnosis of gastroesophageal varices (GEV)Non-inv

6、asive tests (NIT) in the diagnosis of CSPHMonitoring the development of CSPH, varices, high-risk varicesMonitoring changes in HVPG05 Diagnosis and Monitoring05.1Non-invasive tests (NIT) in the diagnosis of CSPH HVPG measurement is the gold-standard method to assess the presence of CSPH, defined as a

7、n HVPG 10 mmHg. CSPH can be identified by non-invasive tests. LS 20-25 kPa, alone or combined with platelet count and spleen size. The presence of porto-systemic collaterals on imaging is sufficient to diagnose CSPH. Patients with gastroesophageal varices on endoscopy have, by definition, CSPH.05.3

8、Monitoring the t of CSPH, , 05.4 Monitoring changes in HVPG-肝硬度、血小板、侧枝血管，若无肝损伤持续因素，每3年查一次胃镜，若有肝损伤持续因素，每2年查一次胃镜.，若无肝损伤持续因素，每2年查一次胃镜，若有肝损伤持续因素，每1年查一次胃镜.，尽管胃镜筛查时没有或是有小静脉曲张，都需要复查胃镜。should not be performed routinely (outside clinical trials). Non-invasive tests do not correlate well with changes in HVPG.

9、Patients with cirrhosis and Patients with cirrhosis and gastroesophageal varices(GEV) c) Patients with cirrhosis and (GEV) d) Patients presenting with acute esophageal e) Patients who have an episode of acute esophageal variceal hemorrhage In patients in the earliest stage of compensated cirrhosis (

10、patients with mild portal hypertension), the objective of treatment is to of CSPH/decompensation and perhaps even to of cirrhosis. is the current mainstay of therapy. Drugs that act on portal flow, such as will be mostly in this sub-stage, as the hyperdynamic circulatory state is not fully developed

11、. and CSPH but In patients with cirrhosis and CSPH but without varices, There is no evidence at present to recommend the use of NSBBs in preventing the formation of varices.（可能有效，证据不足，需要研究） Either traditional (propranolol, nadolol), carvedilol, is recommended for the prevention of first variceal hem

12、orrhage(primary prophylaxis) in patients with medium or large varices (Table 2 for doses and schedules). Patients on NSBB or carvedilol for primary prophylaxis do not require monitoring with serial EGD. Combination therapy NSBB plus EVL is not recommended in this setting. TIPS placement is not recom

13、mended in the prevention of first variceal hemorrhage.c) Patients with compensated cirrhosis and gastroesophageal varices (GEV)is the recommended therapy for patients with high-risk small esophageal varices卡维地洛和卡维地洛和EVL在初级预防中的作用比较在初级预防中的作用比较中中/大食管静脉曲张患者预防首次出血的选择大食管静脉曲张患者预防首次出血的选择EVL NSBB卡维地洛-EVL 与预防

14、静脉曲张首次出血的RCT比较 预防性应用抗生素 血管活性药物. In patients at () who have no contraindications for TIPS, an “early” (preemptive) TIPS within 72 hours from EGD/EVL may benefit selected patients.TIPS作为一线选择TIPS作为二线选择2011 MFMER | 3128596-40Garcia-Pagan et al NEJM 2010In 9 European centers, 63 high-risk patients with a

15、cute variceal bleeding (Child-Pugh C, or B + active bleeding)centrally randomized (within 24h of admission)PTFE-TIPS (10mm)(n=32)(within 24h:19;48h:10; 72h:3)Continue on standard therapy for5 days followed by secondary prophylaxis with BB+IsMn + EBL(n=31) PTFE-TIPS as rescue RxEarly PTFE-TIPS groupD

16、rug + EBL groupAcute Rx: Vasoactive drugs + endoscopic Rx + antibiotics2011 MFMER | 3128596-41Early PTFE-TIPS vs Drug+EBLOverall SurvivalGarcia-Pagan et al. NEJM 2010;362:2370100806040200SurvivalP0.001(log Rank)Early PTFE-TIPS Drugs + EBL 86%60%96%67%6-week1-year18126024Months 最近一个试验显示内镜下急性出血的最近一个试验

17、显示内镜下急性出血的CTPC或或CTPB患者患者应早期行应早期行TIPS 在高风险患者中早期行在高风险患者中早期行TIPS治疗与出血减少正相关治疗与出血减少正相关 本研究证明在高风险患者应施行本研究证明在高风险患者应施行TIPS，即使出血已被内，即使出血已被内镜下控制镜下控制。2011 MFMER | slide-42 For patients in whom an early TIPS is not performed, intravenous vasoactive drugs should be continued for 2-5 days and NSBB initiated once

18、vasoactive drugs are discontinued. Rescue TIPS is indicated in these patients if hemorrhage cannot be controlled or if bleeding recurs despite vasoactive drugs + EVL. In patients in whom TIPS is performed successfully, intravenous vasoactive drugs can be discontinued.06 managemente) Patients who hav

19、e recovered from an episode of acute esophageal varicealhemorrhage Combination of NSBB + EVL is first-line therapy in the prevention of rebleeding . Patients who have a TIPS placed successfully during the acute episode do not require NSBB or EVL. TIPS is the recommended rescue therapy in patients wh

20、o experience recurrent hemorrhage despite combination therapy NSBB + EVL.07 Gastric varicesa) Prevention of first hemorrhage from gastric varicesb) Management of acute hemorrhage from gastric varicesb.1. Endoscopic therapyb.2.Transjugular intrahepatic portosystemic shunt (TIPS)c) Prevention of reble

21、edingc.1. Endoscopic therapy and NSBBsc.2. TIPSc.3. BRTO For prevention of first variceal hemorrhage from can be used,although the data is not as strong as for esophageal varices. Neither TIPS nor BRTO are recommended to prevent first hemorrhage in patients with fundal varices that have not bled.07

22、Gastric varices is the treatment of choice in the control of bleeding from cardiofundal varices). Cyanoacrylate glue injection is an option for cases in which TIPS is not technicallyfeasible, but it is not approved for the treatment of gastric varices in the United States and should be performed onl

23、y in centers where the expertise is available. Patients with acute bleeding from gastric varices should be initially managed in a similar fashion to those bleeding from esophageal varices (using a ). In patients bleeding from arices, either EVL (if technically feasible) orcyanoacrylate glue injectio

24、n, if available, are the recommended endoscopictreatments.07 Gastric varices07 Gastric v In patients who have recovered from a hemorrhage, the combination of (EVL or cyanoacrylate injection) is the first-line therapy to prevent rebleeding. In patients who have recovered from hemorrhage, are first-li

25、ne treatments in the prevention of rebleeding. Cyanoacrylate glue injection is an option for cases in which TIPS or BRTO are not technically feasible, but it is not approved for the treatment of gastric varices in the United States and should be performed only in centers where the expertise is avail

26、able.08 ectopic varices The management of ectopic varices requires a thorough knowledge of the vascularsupply to the varices and a multidisciplinary approach. Options are ligation,cyanoacrylate injection, endosonographic coil placement, TIPS with or without embolization, and BRTO. 具体情况具体对待a) Patient

27、s with refractory ascites or after spontaneous bacterial peritonitis Refractory ascites and spontaneous bacterial peritonitis arefor treatment with these patients, high doses of NSBBs (over 160 mg/day of propranolol or over 80 mg/day of nadolol) should be as they might be associated with worse outco

28、mes. In patients with refractory ascites and severe circulatory dysfunction (systolic blood pressure 90 mmHg, serum sodium 130 meq/L, or hepatorenal syndrome), the dose of NSBBs should be decreased or the drug temporarily held. NSBBs might be reintroduced if circulatory dysfunction improves.b) Patie

29、nts failing may be treated with the combination of or, alternatively, with Randomized trials are required in this group of patients to clarify the best therapeutic strategy.Prevention and treatment of acute variceal bleeding in patients with hepatocellular carcinoma should follow the same principles

30、 as those for patients withouthepatocellular carcinoma09 Special populationsc) Prevention and treatment of variceal bleeding in patients with hepatocellularcarcinoma10 Suggestions for Future Research 1.The role of (eg, liver stiffness, spleen stiffness) in the diagnosis of CSPH in patients with etio

31、logies other than viral/alcoholic cirrhosis 2. The role of noninvasive tests in to different therapies and their relationship to clinical outcomes 3. Prospective studies evaluating the effect of therapies that act on of portal hypertension in the prevention of clinical outcomes other than varices/va

32、riceal hemorrhage. 4. Effects of preventing disease progression in patients with compensated cirrhosis. 5. Role ofodulating the hemodynamic abnormalities of cirrhosis and portal hypertension and the response to medical therapy. 6. Clarify the role ofin the management of acute variceal bleeding, refi

33、ning the target population that will benefit from this treatment. 7. Data on clinical nd other potential targets not yet used clinically in this setting (eg, farnesoid X receptor agonists, enoxaparin). 8.prevention and treatment of bleeding fromTHANKS胃静脉曲张首次出血的处理方案推荐胃静脉曲张首次出血的处理方案推荐NSBBEVL vs 组织胶注射，

34、均有效，但组织胶再出血率低，应用范围广，需新组织胶注射，均有效，但组织胶再出血率低，应用范围广，需新的治疗方法的治疗方法胃静脉曲张出血治疗方案的选择胃静脉曲张出血治疗方案的选择TIPS胃静脉曲张出血治疗的指南推荐胃静脉曲张出血治疗的指南推荐在预防再出血方面，组织胶注射优于在预防再出血方面，组织胶注射优于NSBB，两者联合较组织胶注射单独应用，两者联合较组织胶注射单独应用无优势无优势TIPS较组织胶预防再出血更有效，但肝性脑病发生率高，两者生存率较组织胶预防再出血更有效，但肝性脑病发生率高，两者生存率无差别无差别胃肾分流或脾肾分流中可选用胃肾分流或脾肾分流中可选用BRTO，BRTO后后HVPG1

35、2mmHg可联合可联合TIPS异位曲张静脉需根据来源选择不同治疗方案异位曲张静脉需根据来源选择不同治疗方案Prevention and treatment of acute variceal bleeding in patients with hepatocellular carcinoma should follow the same principles as those for patients withouthepatocellular carcinoma09 Special populationsc) Prevention and treatment of variceal blee

36、ding in patients with hepatocellularcarcinoma10 Suggestions for Future Research 1.The role of noninvasive tests (eg, liver stiffness, spleen stiffness) in the diagnosis of CSPH in patients with etiologies other than viral/alcoholic cirrhosis 2. The role of noninvasive tests in evaluating hemodynamic

37、 response to different therapies and their relationship to clinical outcomes 3. Prospective studies evaluating the effect of therapies that act on pathophysiological mechanisms of portal hypertension in the prevention of clinical outcomes other than varices/variceal hemorrhage. 4. Effects of antifib

38、rotic drugs preventing disease progression in patients with compensated cirrhosis.10 Suggestions for Future Research 5. Role of gut microbiota modulating the hemodynamic abnormalities of cirrhosis and portal hypertension and the response to medical therapy. 6. Clarify the role of preemptive (“early”

39、) TIPS in the management of acute variceal bleeding, refining the target population that will benefit from this treatment. 7. Data on clinical outcomes for statins and other potential targets not yet used clinically in this setting (eg, farnesoid X receptor agonists, enoxaparin). 8. Optimal prevention and treatment of bleeding from cardiofundal varices.